Overall, it would appear that a number of non-HLA susceptibility loci are more specific of ACPA-positive RA (AFF3, CCR6, CCL21, IL2RA, and CD28), some are shared irrespective of the autoantibody serotype (TNFAIP3, C5orf30, STAT4, ANKRD55, BLK, and PTPN22), and others are more associated with autoantibody-negative RA (CLYBL, SMIM2, SPP1, CLEC16A, IRF5, and DCIR) [16,26,27,28,29]. This evidence concerns the gene PTPN22 and rheumatoid arthritis.